Sesquiterpene lactones are a group of secondary plant metabolites consisting of a 15-carbon structure containing an α-methylene-γ-butyrolactone moiety and other additional functional groups. Over the last two to three decades, these terpenoids have received considerable attention due to the broad spectrum of their biological activities, to the plants which produce them, and most importantly, because of their pharmacological effects in humans. About 4,000 of these terpenoids have been isolated and identified, most of them in Asteraceae (Compositae, sunflower family) (Schmidt, Curr. Org. Chem. 1999, 3, 577-608). Some of these plants have been used for centuries in indigenous medical practices in various cultures worldwide.
Parthenolide (1) is a Germacrane sesquiterpene lactone with a unique structure. It has been isolated from several different species in Asteraceae (Compositae) family, feverfew (Tanacetum parthenium) being one of them.

Feverfew has been used to reduce fever and pain and in the treatment of migraine and rheumatoid arthritis (Heptinstall et al., ACS Symposium Series (1998), 691 (Phytomedicines of Europe), 158-175). The active component is parthenolide (1). Recently, it has been revealed that parthenolide (1) can induce tumor apoptosis by the inhibition of NF-κB activities (Cory et al., Anticancer Research 2002, 22, 3805-9; Cory et al., Anticancer Research 2001, 21, 3807-11; Gelfanov et al., Blood, 2000, 98, 2508-17; Kang et al, Brit. J. Pharmacol. 2002, 135, 1235-44; Song et al., J. Asian. Nat. Prod. Res. 2001, 3, 285-91).
Parthenolide (1) is a lipophilic, neutral lactone with low polarity, and has a low water-solubility, limiting its development as a therapeutic agent. Thus, a need exists for the development of soluble parthenolide derivatives that retain their anti-cancer activity.